Ambry to share aggregated anonymous data from 10,000+ human exomes.

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• • Exciting times.
  Firms are starting to be more open with the data they have collected for the benefit of mankind. But do watch out for the fine print. there's a disclaimer that although the data is 'free to download and use, the company retains copyright.'
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  By Andrew Pollack
 
• Posted March 08, 2016

GENETIC TEST FIRM TO MAKE CUSTOMERS’ DATA PUBLICLY AVAILABLE

Original post can be found here.

In an unusual move, a leading genetic testing company is making genetic information from the people it has tested publicly available, a move the company says could make a large trove of data available to researchers looking for genes linked to various diseases.

The company, Ambry Genetics, is expected to announce on Tuesday that it will put information from 10,000 of its customers into a database called AmbryShare.

“We’re going to discover a lot of new diagnostic targets and a lot of new drug targets,” Aaron Elliott, interim chief scientific officer at Ambry, which is based in Southern California, said in an interview. “With our volume, we can pull out a significant number of genes just by the sheer number we are looking at.”

The 10,000 people all have or have had breast or ovarian cancer and were tested by Ambry to see if they have genetic variants that increase the risk of those diseases. Ambry returned to the samples from those customers and, at its own expense, sequenced their exomes — the roughly 1.5 percent of a person’s genome that contains the recipes for the proteins produced by the body.

Since proteins perform most of the functions in the body, sequencing just that part of the genome provides considerable information, and is less expensive than sequencing the entire genome.

AmbryShare will not contain the actual exome of each person, because that would pose a risk to patient privacy. Rather it will contain aggregated data on the genetic variants.

For example, a researcher could look up how frequently a particular mutation occurs among the 10,000 people. Ones that occur frequently in these 10,000 patients, but not among healthy people, could raise the risk of developing those cancers.

Specialists welcomed Ambry’s move, but some said it was unclear how useful the information will be. The Exome Aggregation Consortium, an academic collaboration based at the Broad Institute of M.I.T. and Harvard, already has a similar publicly available database containing information from more than 60,000 exomes.

“It is not clear to me that 10,000 exomes changes the game much,” said David B. Goldstein, professor of genetics at Columbia University.

Ambry said its data would be from people with the diseases it tests for, like epilepsy and intellectual development problems, while the Broad database covers a more general population. Ambry said it hoped to add data from as many as 200,000 customers a year to the database.

The Ambry customers whose data is being used were not told specifically about this project. But in ordering tests they consent to having their samples used for research.

Various labs, including Ambry, have been pooling information on which mutations in certain known breast cancer risk genes are harmful or not. AmbryShare is different — aimed more at novel discoveries of genes linked to diseases.

Data can be valuable to drug companies. The consumer genetics company 23andMe sells access to data from its testing to drug makers and uses that data to develop drugs itself.

Charles Dunlop, founder and chief executive of Ambry, said he was approached by drug companies, but decided to make the company’s data freely available to expedite research.

“I’ve got Stage 4 cancer myself,” he said, referring to advanced prostate cancer that is in remission. “I don’t want to wait an extra day.”

He said Ambry had spent $20 million on the project. Ambry is privately held and majority-owned by Mr. Dunlop and his family, insulating it somewhat from shareholder pressure.

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Correction: March 10, 2016 

An earlier version of this article described incorrectly the step that Ambry is taking with its customers’ data. It is making the data publicly available; it is not putting the data in the public domain. While the data is free to download and use, the company retains copyright.

Baylor releases Exome and WGS data of 7 cancer patients with Open Access

An open access pilot freely sharing cancer genomic data from participants in Texas

• Scientific Data 3, Article number: 160010 (2016) 
• ​doi:10.1038/sdata.2016.10
•  In a pilot Open Access (OA) project from the CPRIT-funded Texas Cancer Research Biobank, many Texas cancer patients were willing to openly share genomic data from tumor and normal matched pair specimens. For the first time, genetic data from 7 human cancer cases with matched normal are freely available without requirement for data use agreements nor any major restriction except that end users cannot attempt to re-identify the participants (http://txcrb.org/open.html).

There's whole exome seq data and 2 whole genome sequencing data where the sample quality is good enough for WGS.

A copy of the open-access TCRB data, conditions of use, and the HGSC’s Mercury informatics pipeline is available now for DNAnexus Platform users.

The full paper is here http://www.nature.com/articles/sdata201610

A copy of the data is also available for DNAnexus Platform users here https://dnanexus.github.io/tcrb-data/

Fancy new interactive visualization of coverage depth for exome sequencing. http://t.co/3a61F4OdKY

Fancy new interactive visualization of coverage depth for exome sequencing.http://t.co/3a61F4OdKY

This has to appeal to the biologists ...

samtools upgrade for exome & target region SNP calling

off the samtools helplist, a new feature that's very helpful for exome / target region NGS studies

BTW, samtools is now able to compute read depth and call SNPs in regions specified by an input BED file. For both "samtools mpileup" (not pileup) and "bcftools view", you may provide the BED via the "-l" option. If the input has two numeric columns, it is parsed as a BED (region list); if has one numeric column, parsed as a position list file, so the "-l" option is backward compatible with old versions. It is also possible to retrieve alignments overlapping a BED file with 

samtools view -L in.bed 

. For mpileup, using "-l" to call SNPs in target/exome regions can be much faster than doing whole-genome calling and then filtering.

Heng

Exome sequencing reveals mutations in previously unconsidered candidate genes

Excerpted from Bio-IT World 

December 20, 2010 | Doctors at the Medical College in Wisconsin have published in the journal Genetics and Medicine the results of exome sequencing in a seriously ill boy with undiagnosed bowel disease. The study (using 454 sequencing) revealed mutations in a gene called XIAP, which interestingly was not previously considered among more than 2,000 candidate genes before the DNA sequencing was performed. ....read full article

Exome Sequencing hints at sporadic mutations as cause for mental retardation.

1st spotted off Genomeweb
NEW YORK (GenomeWeb News) – De novo mutations that spring up in children but are absent in their parents are likely the culprit in many unexplained cases of mental retardation, according to a Dutch team.
Using exome sequencing in 10 parent-child trios, the researchers found nine non-synonymous mutations in children with mental retardation that were not found in their parents, including half a dozen mutations that appear to be pathogenic. The research, which appeared online yesterday in Nature Genetics, hints at an under-appreciated role for sporadic mutations in mental retardation — and underscores the notion that mental retardation can stem from changes in a wide variety of genes.

 I think it's fascinating to find so many new mutations and changes in DNA that may affect one's quality of life, simply by sequencing the coding regions (and not all of it if I may add). This paper is fascinating as it raises the question if deleterious sporadic mutations are unlikely culprits for a whole variety of diseases that have a genetic risk.
it is certainly more likely that such an event will occur in coding regions but I do not doubt that for some diseases, perhaps the non-coding regions (that play a regulatory role) might have the same effect. If it was a clear cut mutation that results in a dysfunctional protein, and there's no redundancy in the system, it is likely the system will crash. whereas, if it was changes in the expression levels, it might lead to a slightly wobbly system that just doesn't function as well.

While everyone else is waiting for Whole Genome Sequencing to drop in price. There are groups already publishing with exome data. I think in 6 months time, we will see more WGS papers coming up... It's an exciting time for Genomics science!

See the full paper below

A de novo paradigm for mental retardation Nature Genetics | Letter

 

US clinics quietly embrace whole-genome sequencing @ Nature News

read the full article
As hospitals and insurers battle over coverage for single-gene diagnostic tests, and the US Food and Drug Administration cracks down on the products of personal genomics companies, a growing number of doctors are relying on the sequencing of either the whole genome or of the coding region, known as the exome.
"If one hospital is doing it, you can be sure others will start, because patients will vote with their feet," Elizabeth Worthey, a genomics specialist at the Human and Molecular Genetics Center (HMGC) of the Medical College of Wisconsin in Milwaukee, said at the Personal Genome meeting at Cold Spring Harbor Laboratory in New York last weekend.
In May 2009, the genetic-technology provider Illumina, based in San Diego, California, launched its Clinical Services programme with two of its high-throughput genome analysers. The company now has 15 such devices dedicated to this programme.
Illumina provides the raw sequence data attained from a patient's DNA sample to a physician, who passes it on to a bioinformatics team, which works to crack the patient's condition. However, Illumina is working to develop tools to help physicians navigate genomes and identify genes already associated with diseases, as well as novel ones.
So far, the company has sequenced more than 24 genomes from patients with rare diseases or atypical cancers at the request of physicians at academic medical centres. The standard US$19,500 price tag is typically covered by the patient, by means of a research grant, or with the help of private foundations, although one patient is currently applying for insurance reimbursement. 

I would be really surprised if insurance is able to cover for exome sequencing in any conditions. Also see my Commentary on Personal Genomics testing

Knome invites researchers to apply for free sequencing and analysis of human exomes

I think there's nothing like the word 'free' that gets researchers to stand up and listen ;p

The 2010 KnomeDISCOVERY Research Awards
Knome invites researchers to apply for free sequencing and analysis of human exomes

Knome announces the launch of the KnomeDISCOVERY Research Awards, designed to spur novel discoveries by researchers working at the nexus of genomics and human health. Given annually, the KnomeDISCOVERY Research Awards will fund innovative projects that help reveal the genetic underpinnings of disease.

This year, Knome will award comprehensive sequencing and discovery-supportive analysis of a total of six (6) human exomes. These services will be distributed among three winning biomedical research groups, each of whom will use the award to study a pair of human exomes of their choice in order to answer a compelling biological question.